1. Field of the Invention
The present invention relates generally to the field of molecular biology and medicine. More particularly, it concerns antimicrobial compositions comprising a glyceryl nitrate.
2. Description of Related Art
Currently, compositions for biofilm eradication where contact with humans or animals can occur generally require high alcohol concentrations, antibiotics and/or relatively toxic concentrations of antiseptic agents. Antibiotics are often expensive and their prophylactic use is problematic due to the potential for inducing antimicrobial resistance.
Vascular catheters are currently hydraulically locked with saline or heparin solutions between infusions or blood sampling through lumens. The hydraulically locked lumens are generally capped off between uses. Lumens can become contaminated with bacteria or fungi through introduction of contaminated infusates, by environmental exposure when uncapped, or through manual contact with luers and/or caps. In the case of suspected bloodstream infections for catheterized patients, disinfection and salvage of the catheter with an antimicrobial lock can be employed. Antibiotic lock solutions are frequently used but have the disadvantages of being expensive and risking the development of antibiotic-resistant organisms. Infections from antibiotic resistant organisms typically have higher treatment costs and mortalities. High concentration ethanol solutions have also been attempted. Flushing of a 70% ethanol lock solution did not produce a significant reduction in infection and was associated with a higher indigence of non-severe complaints associated with inebriation (Slobbe et al., Prevention of Catheter-Related Bacteremia with a Daily Ethanol Lock in Patients with Tunneled Catheters: A Randomized, Placebo-Controlled Trial, PLoS ONE 5(5): e10840). A prophylactic clinical trial involving 1-3 hours of locking with 50% ethanol was not effective in reducing infection in hospitalized patients with long-term catheters (Crnich et al., Prospective Randomized Double-Blind Trial of an Ethanol Lock for Prevention of CLABSI [Abstract]. In: 49th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, USA. 2009).
Microorganisms present in biofilms can be particularly difficult to eradicate. Biofilm phenotypes are important in recalcitrant device-associated and nosocomial infections and are much more difficult to eradicate than microbes in the dilute planktonic state. Biofilm formation is often an important part of generating an infection by a bacterial or fungal organism. In addition, biofilm formation can cause odor, discoloration, degradation and other significant problems by fouling pipes and other industrial equipment. One medical application of particular interest is disinfection of the lumenal surfaces of vascular catheters. Intralumenal infections are a significant problem for long term catheterized patients who require vascular access for infusion of medications or nutrition. In between catheter uses, the lumens of the catheters are typically locked with saline or heparin-saline solutions to prevent blood from clotting and occluding the lumens. Through the course of handling during access procedures or through use of contaminated infusates catheter lumens can become colonized by pathogenic organisms and can become a source of bacteremias or candidemias. Lumenal sourced colonization is the most common cause of late-onset catheter-associated blood stream infections. Clearly, there is a need for new antimicrobial compositions that may be used to kill microorganisms present in biofilms.